The size of nanodrugs plays a crucial role in shaping their chemical and physical characteristics,consequently influencing their therapeutic and diagnostic interactions within biological systems.The optimal size of na...The size of nanodrugs plays a crucial role in shaping their chemical and physical characteristics,consequently influencing their therapeutic and diagnostic interactions within biological systems.The optimal size of nanomedicines,whether small or large,offers distinct advantages in disease treatment,creating a dilemma in the selection process.Addressing this challenge,size-transformable nanodrugs have surfaced as a promising solution,as they can be tailored to entail the benefits associated with both small and large nanoparticles.In this review,various strategies are summarized for constructing size-transformable nanosystems with a focus on nanotherapeutic applications in the field of biomedicine.Particularly we highlight recent research developments in cancer therapy.This review aims to inspire researchers to further develop various toolboxes for fabricating size-transformable nanomedicines for improved intervention against diverse human diseases.展开更多
There are several limitations to the application of nanoparticles in the treatment of cancer,including their low drug loading,poor colloidal stability,insufficient tumor penetration,and uncontrolled release of the dru...There are several limitations to the application of nanoparticles in the treatment of cancer,including their low drug loading,poor colloidal stability,insufficient tumor penetration,and uncontrolled release of the drug.Herein,gelatin/laponite(LP)/doxorubicin(GLD)nanoparticles are developed by crosslinking LP with gelatin for doxorubicin delivery.GLD shows high doxorubicin encapsulation efficacy(99%)and strong colloidal stability,as seen from the unchanged size over the past 21 days and reduced protein absorption by 48-fold compared with unmodified laponite/doxorubicin nanoparticles.When gelatin from 115 nm GLD reaches the tumor site,matrix metallopeptidase-2(MMP-2)from the tumor environment breaks it down to release smaller 40 nm LP nanoparticles for effective tumor cell endocytosis.As demonstrated by superior penetration in both in vitro three-dimensional(3D)tumor spheroids(138-fold increase compared to the free drug)and in vivo tumor models.The intracellular low pH and MMP-2 further cause doxorubicin release after endocytosis by tumor cells,leading to a higher inhibitory potential against cancer cells.The improved anticancer effectiveness and strong in vivo biocompatibility of GLD have been confirmed using a mouse tumor-bearing model.MMP-2/pH sequentially triggered anticancer drug delivery is made possible by the logical design of tumor-penetrating GLD,offering a useful method for anticancer therapy.展开更多
Heart failure resulting from myocardial infarction(MI)is a leading global health concern.Current revasculari-zation therapies cannot fully restore the infarcted myocardium or prevent maladaptive ventricular remodeling...Heart failure resulting from myocardial infarction(MI)is a leading global health concern.Current revasculari-zation therapies cannot fully restore the infarcted myocardium or prevent maladaptive ventricular remodeling.Traditional Chinese medicine with its multitarget regulation and favorable biosafety shows a promising thera-peutic potential.Tanshinone IIA(TIIA)and formononetin(FM),two bioactive compounds derived from Salvia miltiorrhiza and Astragalus membranaceus,respectively,exhibit antioxidant,anti-inflammatory,and proangio-genic effects.Herein,a neutrophil-targeted nanomedicine(TF-5NP)was developed to deliver TIIA and FM to the infarcted myocardium for mitigating oxidative damage and promoting angiogenesis.TF-5NP was synthesized by coassembling bis-5-hydroxytryptamine-modified 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-poly-ethylene glycol-carboxylic acid with cholesterol and lipid 1,2-distearoyl-sn-glycero-3-phosphoglycerol,which binds to troponin in the infarcted myocardium.This nanomedicine reduces inflammation and cardiomyocyte damage and improves cardiac function in porcine MI models,with therapeutic effects lasting for~28 d.These findings suggest that TF-5NP use is a promising approach for treating post-MI maladaptive remodeling and heart failure.展开更多
基金supported in part by Startup and Retention Funds from the R.Ken Coit College of Pharmacy at The University of Arizona(UArizona),a PhRMA Foundation Faculty Starter Grant in Drug Delivery,UArizona Cancer Center Internal Pilot Award,and the National Institutes of Health(NIH)grants(R35GM147002 and R01CA272487).
文摘The size of nanodrugs plays a crucial role in shaping their chemical and physical characteristics,consequently influencing their therapeutic and diagnostic interactions within biological systems.The optimal size of nanomedicines,whether small or large,offers distinct advantages in disease treatment,creating a dilemma in the selection process.Addressing this challenge,size-transformable nanodrugs have surfaced as a promising solution,as they can be tailored to entail the benefits associated with both small and large nanoparticles.In this review,various strategies are summarized for constructing size-transformable nanosystems with a focus on nanotherapeutic applications in the field of biomedicine.Particularly we highlight recent research developments in cancer therapy.This review aims to inspire researchers to further develop various toolboxes for fabricating size-transformable nanomedicines for improved intervention against diverse human diseases.
基金supported by the National Basic Research Program of China(973 Program,No.2012CB933600)the National Natural Science Foundation of China(Nos.81771964 and 82072051)+4 种基金the Shanghai Municipal Natural Science Foundation(No.15ZR1408500)funded by the Special Project of Clinical Research of Health Industry of Shanghai Municipal Health Commission(No.201940178)the Scientific Research Project of Hongkou District Health Committee of Shanghai(No.2002-17)the Clinical Research Project of Wu Jieping Medical Foundation(No.320.6750.2020-18-2)the Research Project of Shanghai Fourth People’s Hospital(No.sykyqd 00701&00702).
文摘There are several limitations to the application of nanoparticles in the treatment of cancer,including their low drug loading,poor colloidal stability,insufficient tumor penetration,and uncontrolled release of the drug.Herein,gelatin/laponite(LP)/doxorubicin(GLD)nanoparticles are developed by crosslinking LP with gelatin for doxorubicin delivery.GLD shows high doxorubicin encapsulation efficacy(99%)and strong colloidal stability,as seen from the unchanged size over the past 21 days and reduced protein absorption by 48-fold compared with unmodified laponite/doxorubicin nanoparticles.When gelatin from 115 nm GLD reaches the tumor site,matrix metallopeptidase-2(MMP-2)from the tumor environment breaks it down to release smaller 40 nm LP nanoparticles for effective tumor cell endocytosis.As demonstrated by superior penetration in both in vitro three-dimensional(3D)tumor spheroids(138-fold increase compared to the free drug)and in vivo tumor models.The intracellular low pH and MMP-2 further cause doxorubicin release after endocytosis by tumor cells,leading to a higher inhibitory potential against cancer cells.The improved anticancer effectiveness and strong in vivo biocompatibility of GLD have been confirmed using a mouse tumor-bearing model.MMP-2/pH sequentially triggered anticancer drug delivery is made possible by the logical design of tumor-penetrating GLD,offering a useful method for anticancer therapy.
基金supported by the National Natural Science Founda-tion of China(Grant Nos.82274271&82104962&82004112)Guang-dong Basic and Applied Basic Research Foundation(Grant Nos.2024B1515020033&2024A1515011686&2023A1515220029)+6 种基金Outstanding Young Talents Youth Program of Guangdong Hospital of Chinese Medicine(Grant No.SZ2023QNO1)Guangzhou Science and Technology Fund(202201020565)Major Science and Technology Projects of Chinese Medicine in Guangzhou Region(2025CX010,2025QN010)the 2023 Young Top Talent Cultivation“Unveiling the List of Commander-in-Chief”Project Program of Guangzhou University of Chinese Medicine(to Shuai MAO)Project of State Key Laboratory of Dampness Syndrome of Chinese Medicine,The Second Affiliated Hos-pital of Guangzhou University of Chinese Medicine(SZ2024KF01)Guangzhou Science and Technology Plan(2024A04J3304)Guangzhou Municipal Science and Technology Bureau-Academia Joint Funding Program(2024A03J0062).
文摘Heart failure resulting from myocardial infarction(MI)is a leading global health concern.Current revasculari-zation therapies cannot fully restore the infarcted myocardium or prevent maladaptive ventricular remodeling.Traditional Chinese medicine with its multitarget regulation and favorable biosafety shows a promising thera-peutic potential.Tanshinone IIA(TIIA)and formononetin(FM),two bioactive compounds derived from Salvia miltiorrhiza and Astragalus membranaceus,respectively,exhibit antioxidant,anti-inflammatory,and proangio-genic effects.Herein,a neutrophil-targeted nanomedicine(TF-5NP)was developed to deliver TIIA and FM to the infarcted myocardium for mitigating oxidative damage and promoting angiogenesis.TF-5NP was synthesized by coassembling bis-5-hydroxytryptamine-modified 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-poly-ethylene glycol-carboxylic acid with cholesterol and lipid 1,2-distearoyl-sn-glycero-3-phosphoglycerol,which binds to troponin in the infarcted myocardium.This nanomedicine reduces inflammation and cardiomyocyte damage and improves cardiac function in porcine MI models,with therapeutic effects lasting for~28 d.These findings suggest that TF-5NP use is a promising approach for treating post-MI maladaptive remodeling and heart failure.
